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T315I mutated patient

  • M.D. Figen Atalay
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1 month 6 days ago - 4 weeks 1 day ago #1984 by M.D. Figen Atalay
T315I mutated patient was created by M.D. Figen Atalay
Location - Turkey.

A 62-year-old female patient has been using ponatinib 15 mg for 7 years due to T315I mutation. I have been following her for 5 years in the case of Complete Molecular Response. However, in the last year, the patient has developed hypertensive attacks, stent placement due to carotid artery stenosis, and finally peripheral neuropathy at CTC 2. The patient complains that her quality of life has deteriorated. My question to you is; should I consider switching to asciminib treatment in this patient or should I stop ponatinib treatment for TFR and perform close molecular follow-up. Or should I consider Allogeneic transplantation in a patient with Complete Molecular Response? Thank you in advance for your suggestions. Best regards.
Last edit: 4 weeks 1 day ago by arlene.
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  • Kendra Sweet
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4 weeks 1 day ago #1985 by Kendra Sweet
Replied by Kendra Sweet on topic T315I mutated patient
For the patient described below, I would recommend switching to Asciminib 200mg PO BID. Although it is tempting to try TFR, that is not something we typically recommend for patients with T315I on ponatinib. I don’t think the patient needs to proceed to transplant. I think that Asciminib should be a great option.
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  • MIkhail Fominykh, MD, PhD
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4 weeks 20 hours ago #1986 by MIkhail Fominykh, MD, PhD
Replied by MIkhail Fominykh, MD, PhD on topic T315I mutated patient
This is a very tough and uncommon clinical case. I cannot remember the article about TFR in T315I-mutation patients, they are in a high-risk group, which would be non-safety and challenging in this situation.
In my opinion, the first option is the de-escalation of Ponatinib to 10 mg due to cardiovascular problems with close monitoring of BCR::ABL.
The second option is switching to Asciminib. The allo-HSCT in this clinical case would be the last option as a reserve.
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  • Massimo Breccia
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4 weeks 17 hours ago #1987 by Massimo Breccia
Replied by Massimo Breccia on topic T315I mutated patient
In this case I would recommend a switch to asciminib. Considering T315I mutation, this patient is not candidate to TFR.
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  • Katia Pagnano
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4 weeks 16 hours ago #1988 by Katia Pagnano
Replied by Katia Pagnano on topic T315I mutated patient
I would also switch to asciminib but would consider a TFR attempt first as a possibility, there are some data of sucessful TFR with ponatinib, although in patients with T315I the experience is limited. doi.org/10.1182/blood-2023-187230
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  • Jane Apperley
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3 weeks 5 days ago #1989 by Jane Apperley
Replied by Jane Apperley on topic T315I mutated patient
We had a very similar situation some years ago in a woman in her 70s. She had originally been in PACE, and after several years on ponatinib she developed PAOD. She had been molecularly undetectable for a couple of years. We had no alternative but to stop treatment. She is now in her 80s, fit and well, off treatment since 2017

It would be entirely reasonable to stop, continue molecular monitoring and introduce asciminib if there is evidence of recurrence
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